Retinal degeneration is a very common clinical feature in ciliopathies, a group of rare genetic disorders originating from a defect in the primary cilium, an organelle ubiquitously expressed in the human body. The photoreceptor cell is structured with two segments connected by a modified cilium, the so-called connecting cilium that acts as a protein highway allowing protein transport between the two segments required for efficient light detection and transduction. Ciliopathies therefore impact protein transport from the inner to the outer segment and backwards, inducing retinitis pigmentosa. The onset is usually during early childhood and leads to major visual impairment early on with a major impact on everyday life and social integration.
This retinal degeneration mechanism is observed either in isolated retinitis pigmentosa (such as Leber's Congenital Amaurosis or X-linked retinitis pigmentosa) or also in syndromic conditions like Bardet-Biedl Syndrome (BBS) or Alström syndrome (ALMS), both emblematic ciliopathies cardinally characterized by retinitis pigmentosa. Among all the biological processes that can be implied, a defect in the functioning of the connecting cilia represents more than 20% of all cases of retinitis pigmentosa, which is overall a very high rate for a common pathogenesis mechanism.
Treatment for inherited retinal dystrophies has progressed at a regular speed in the last decade. However, presently there is no curative approach available and no satisfactory palliative approach that actually helps to preserve the vision or at least slow the retinal defects. Treatments mainly focus on reducing the symptoms (tinted glasses, low vision aids) and preventing the complications (cataract surgery, cystoid macular edema).
To date, a dozen studies or trials are declared and currently under way using various approaches: pharmacological, tissue engineering, gene therapy and prosthetic devices. Gene therapy is one of the most advanced fields to date as trials are currently being performed on human beings in various countries, especially for the most emblematic RPE65 gene therapy projects. Due to the high genetic heterogeneity and the multiple biological pathways involved in retinitis pigmentosa, the diversity of strategies to find treatment remains pertinent. A couple of gene therapy projects for ciliopathy related retinal degenerations are currently being undertaken: RPGR in dogs (Beltran et al., 2011) and BBS4 in mice (Simons et al., 2011).
However, the retinal degeneration occurs in most cases very early in childhood and early gene therapy injections may be dangerous in terms of inflammatory reactions known to be acute in very young children. Accordingly, there is a significant need for a pharmacological treatment that could slow the retinal degeneration for preserving the photoreceptor cells in various ciliopathies and postponing the use of gene therapy.